CHANGES IN HEMOSTATIC VARIABLES INDUCED BY ORAL-CONTRACEPTIVES CONTAINING 50 MU-G OR 30 MU-G ESTROGEN - ABSENCE OF DOSE-DEPENDENT EFFECT ONPAI-1 ACTIVITY

Several studies have suggested a dose-response relation between the oe strogen content of oral contraceptive (OC) and the risk of both venous thrombosis and arterial disease, when oestrogen doses were higher tha n 50 mu g However, there is no clear epidemiological evidence for a de crease in thrombotic risk with formulations containing less than 50 mu g oestrogen. Therefore, we investigated haemostatic variables in user s of OC containing either 30 mu g (35 women) or 50 mu g (29 women) eth inyl estradiol as compared with non users (64 women) matched for age a nd smoking status. Mean values of antithrombin activity were significa ntly lower in 30 mu g or 50 mu g oestrogen users than in non users (96 % and 98% vs 105%, respectively, p<0.001), but they were not significa ntly different between the two groups of OC users. There was a signifi cant increase in mean values of factor VII antigen in women taking eit her 30 mu g or 50 mu g oestrogen as compared with non users (96% and 1 01% vs 85%, respectively, p<0.005). Although the difference between bo th groups of OC users was not significant, a positive linear trend in factor VII levels was observed within the 0-50 mu g oestrogen range (p <0.001). Mean levels of fibrinogen were slightly higher in 30 mu g or 50 mu g oestrogen users than in non users (2.71, 2.66 g/l vs 2.55 g/l, respectively,), but there was no significant difference between the t hree groups. Mean values of PAI-1 activity were significantly lower in both groups of OC users than in non users (4.89 and 4.63 AU/ml vs 6.4 7 AU/ml, respectively, p<0.02), but this decrease was not dose-depende nt. There was no significant difference in haemostatic variables betwe en 30 mu g oestrogen preparations containing either 100 mu g (13 women ), 150 mu g (3 women) or 200 mu g (19 women) levonorgestrel. In 50 mu g oestrogen preparations, the wide range of different types of progest ogens did not allow valid assessment of progestogens effect. These dat a provide further evidence for an alteration of blood coagulation and fibrinolysis in OC users within the 30 mu g-50 mu g oestrogen range. H owever, despite a possible dose-dependent effect of oestrogen on facto r VII? our results suggest no substantial change in PAI-1 activity and other markers of thrombogenic risk when oestrogen content of combined OC is decreased from 50 mu g to 30 mu g. The potential role of proges togens in haemostatic system needs further investigations.